While protein typically forms a specific native structure through folding to play a role in biological functions, it may aggregate into a fiber including many β-sheet structures (amyloid formation) through misfolding. Aggregates (oligomers, protofibrils, fibers) produced in the course of the amyloid formation are known to cause various functional disorders (such diseases are collectively referred to as “amyloid diseases”), and 20 or more proteins have been identified as causal substances for amyloid diseases. Known examples of such amyloid include amyloid β for Alzheimer's disease, tau protein, α-synuclein for Parkinson's disease, amylin for diabetes mellitus, transthyretin for systemic amyloidosis, and huntingtin for Huntington's disease.
With regard to development strategy for therapeutic drugs targeting these pathogenic amyloids, known examples for the case of amyloid β (abbreviated as “Aβ”), which is a causal amyloid for Alzheimer's disease, include an inhibitor for an enzyme which produces Aβ from a precursor protein, an accelerator for an Aβ-degrading enzyme, immunotherapy, and an inhibitor for Aβ aggregation.
Previous studies on Aβ have reported that a small quantity of an Met-oxygenated form of Aβ peptide (an oxygenated form with the sulfur atom of an Met residue in Aβ peptide oxygenated (O)) remains in the living body, and that the Met-oxygenated form has lower aggregability than the Aβ peptide (Non Patent Literatures 1 to 3). From these viewpoints, the present inventors have reported that oxygenation of Aβ peptide by using a flavin photocatalyst having an Aβ-binding site represented by a formula (a) provides an oxygenated form of Aβ peptide, and the oxygenated form of Aβ peptide suppresses the aggregation of Aβ (Non Patent Literature 4).
